The human cytomegaloviruses (CMV) are capable of causing a variety of clinical disease states ranging from asymptomatic infection to production of severe congenital defects and death of the host. I propose to study the molecular biology of human CMV infections including the molecular organization of the human CMV genome, the interaction of CMV with cells during permissive and nonpermissive infections, and the oncogenic transformation of cells by CMV. In particular, I will focus on the nature and association of the viral DNA with the cellular genome and on the regulation and characteristics of the virus-specific transcription and translation products. For these studies, I will use a wide variety of molecular techniques including physico-chemical analyses of DNA, fragmentation of DNA with restriction endonucleases, the DNA transfer procedure of Southern, the RNA transfer procedure of Alwine et al., nucleic acid hybridization with highly defined reagents, the immuno-precipitation of viral proteins from infected cells, and the cell-free translation of viral RNA. The major objectives of the research proposed are 1) to define thoroughly the molecular biology of human CMV infections in permissive cells, 2) to characterize the molecular events occurring during nonpermissive infections and their relationship to possible mechanisms of latency, and 3) to determine the oncogenic potential of human CMV.